CN101416957A - Use of resveratrol or naringenin in preventing and treating diabetic nephropathy - Google Patents
Use of resveratrol or naringenin in preventing and treating diabetic nephropathy Download PDFInfo
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- CN101416957A CN101416957A CNA2008102391451A CN200810239145A CN101416957A CN 101416957 A CN101416957 A CN 101416957A CN A2008102391451 A CNA2008102391451 A CN A2008102391451A CN 200810239145 A CN200810239145 A CN 200810239145A CN 101416957 A CN101416957 A CN 101416957A
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- naringenin
- resveratrol
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- diabetes
- diabetic nephropathy
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- WGEYAGZBLYNDFV-UHFFFAOYSA-N naringenin Natural products C1(=O)C2=C(O)C=C(O)C=C2OC(C1)C1=CC=C(CC1)O WGEYAGZBLYNDFV-UHFFFAOYSA-N 0.000 title claims abstract description 49
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Abstract
The invention discloses the application of resveratrol and naringenin, particularly the application of the resveratrol and the naringenin in restraining the level increasing of the transforming growth factor Beta 1 in the human body and preparing medicines used for preventing or treating diabetes and nephropathy.
Description
Technical field
The present invention relates to the application of resveratrol or naringenin, be particularly related to resveratrol or naringenin by reducing the application of level in prevention and treatment diabetic nephropathy of transforming growth factor-beta 1 in the body (transforming growth factor betal is called for short TGF-β 1).
Background technology
There is the trend of increasing in the following 10 years whole world of onset diabetes rate, and wherein life-threatening diabetic nephropathy is the leading reason of western countries' diabetes death, is also just becoming the following diabetes main causes of death of Asia and developing country.Current, the measure that reduces diabetic nephropathy danger mainly is the albumen picked-up in strict blood sugar control, hypertension and the dietary restriction etc., can reduce by the 20% death risk rate that is caused by renal failure.
Diabetic nephropathy shows as glomerule function and structural change, comprises that glomerular filtration increases, glomerular basement membrane thickening, extracellular matrix extend to glomerular mesangium zone etc.In addition, the renal tubules pathological changes is also very outstanding in 1/3rd type ii diabetes patient.Clinical and zoopery proves that all the development of TGF-β and diabetic nephropathy syndrome is closely related, TGF-β mRNA and protein level thereof are all expressed rising in clinical discovery diabetic nephropathy patient glomerule and the renal tubules chamber, in inductive diabetes rat of streptozotocin and the mouse kidney, the rising of TGF-β mRNA expression and protein level thereof is also arranged, during cell in vitro was cultivated, high sugar also all had the TGF-of stimulation β rising effect to the various kinds of cell system that derives from glomerule and renal tubules chamber.In addition, transduceed and express TGF-β and can make mice that serious renal damage takes place, followed renal fibrosis simultaneously; Also make mice the progressivity renal damage occur at the liver expression TGF-β 1 that transduceed, have the activation TGF-β 1 of higher concentration simultaneously in the blood.On the contrary, stop TGF-β can improve the diabetes organ injury of mice with antibody or antisense RNA measure.
Resveratrol and naringenin are ubiquitous effective ingredient in the plant, and especially content is higher in Fructus Vitis viniferae and manufactured goods thereof, have multiple pharmacological effect such as antibiotic, antiinflammatory, removing free radical, antitumor.But also do not find the effect that resveratrol, naringenin have the level that can reduce TGF-β 1 in diabetic mice serum and the renal tissue and alleviate the diabetic mice kidney damage in the prior art.
Summary of the invention
One object of the present invention is the application of open resveratrol and naringenin; Another object of the present invention is that open resveratrol and naringenin suppress the application that the transforming growth factor-beta 1 level raises and prevents or treat diabetic nephropathy in the body.
The present invention has disclosed the application in the rising of TGF-β 1 level in the body that the reduction diabetes cause of natural flavonoid micromolecular compounds such as resveratrol, naringenin, and in the application that prevents and treat diabetic nephropathy.
Description of drawings
Fig. 1: flavone compounds such as resveratrol and naringenin are to the influence of diabetic mice serum TG F-β 1
Fig. 2: flavone compounds such as resveratrol and naringenin are to the influence of diabetic mice kidney TGF-β 1
Fig. 3: flavone compounds such as resveratrol and naringenin are to the influence of alloxan type I blood glucose in diabetic mice
Fig. 4: flavone compounds such as resveratrol and naringenin are to the influence of streptozotocin type ii diabetes mouse blood sugar
Fig. 5: flavone compounds such as resveratrol and naringenin are to the influence of alloxan type i diabetes mice amount of drinking water
Fig. 6: flavonoids such as resveratrol and naringenin are to the influence of streptozotocin type ii diabetes mice dietary amount
Fig. 7: flavonoids such as resveratrol and naringenin are to the influence of type i diabetes mice creatinine clearance rate
Fig. 8: flavonoids such as resveratrol and naringenin are to the albuminous influence of type i diabetes mouse retention
Fig. 9: flavonoids such as resveratrol and naringenin are to the preventive effect of I type and type ii diabetes
Figure 10: flavone compounds such as resveratrol and naringenin are to the influence of normal mouse sugar dosis tolerata
Below animal experiment study further illustrate that resveratrol and naringenin suppress the useful effect that TGF-β 1 is used for prevention and treatment diabetic nephropathy among the present invention:
Experimental example 1 resveratrol and naringenin etc. are done the treatment of the mouse type i diabetes that alloxan is induced With.
Experimental technique: with alloxan 80mg/kg tail vein injection in the kunming mice of body weight 20 ± 1g, 1 time weekly, inject altogether 2 times. In 1 week after the last injection, fasting blood-glucose is measured in the tail end blood sampling, with empty stomach Blood sugar is the type i diabetes mouse greater than the mouse of 13mmol/L.
To be selected in mice by blood glucose height random packet: model control group: intravenous injection or irritate stomach and wait the capacity solvent; Treatment group: gastric infusion, resveratrol 50mg/kg, the equal 100mg/kg of naringenin, naringin, hesperetin, genistein and luteolin, every group of 10 mices, male and female half and half, food-intake and the amount of drinking water of mice are measured in administration every day 1 time every day, draw the dietary amount weekly of mice, the change curve of amount of drinking water, continuous 10 weeks.The 6th week, the 10th week are respectively surveyed 1 fasting glucose (more than the fasting 12h) when treatment finishes, when finishing, treatment detects creatinine renal clearance and urinaryalbumin content to estimate kidney damage, eye socket venous blood collection separation of serum afterwards, subsequently mice is put to death, the excision kidney is used to survey tissue T GF-β 1 with centrifuging and taking supernatant after the PBS homogenate.Serum and tissue T GF-β 1 usefulness ELISA test kit detect, urinaryalbumin content immunization powder firing rate rate turbidimetry kit measurement, serum creatinine amount alkaline picric acid method kit measurement.
The result: flavone compounds such as resveratrol and naringenin can reduce alloxan inductive type i diabetes mice mice serum and kidney TGF-β 1 (seeing Fig. 1 and Fig. 2).6 kinds of natural flavonoid micromolecular compounds also reduce the inductive type i diabetes mouse blood sugar of alloxan (see figure 3), improve type i diabetes mice polydipsia polyphagia symptom (seeing Fig. 5 and Fig. 6), and improve type i diabetes mice creatinine clearance rate and reduce urinaryalbumin content, thereby alleviate diabetic mice kidney damage (seeing Fig. 7 and Fig. 8).
Above result shows that flavone compounds such as resveratrol and naringenin have therapeutical effect to inductive mice type i diabetes of alloxan and complication.
Experimental example 2 resveratrols and naringenin etc. are to the therapeutical effect of the inductive type ii diabetes of streptozotocin
Experimental technique: in the C57BL/6 of body weight 20 ± 1g mice, lumbar injection nicotiamide 100mg/kg 1 time weekly, injects 3 times altogether simultaneously with streptozotocin 100mg/kg tail vein injection.In last injection 1 week of back, fasting glucose is measured in the tail end blood sampling, is the type ii diabetes mice with fasting glucose the mice of 9-12mmol/L.
To be selected in mice by blood glucose height random packet: model control group: intravenous injection or irritate stomach and wait the capacity solvent; Treatment group: gastric infusion, resveratrol 50mg/kg, the equal 100mg/kg of naringenin, naringin, hesperetin, genistein and luteolin, every group of 10 mices, male and female half and half, administration every day 1 time, continuous 8 weeks.The 5th week, the 8th week are respectively surveyed 1 fasting glucose (more than the fasting 12h) when treatment finishes, eye socket venous blood collection separation of serum was put to death mice subsequently when treatment finished, and the excision kidney is used to survey tissue T GF-β 1 with centrifuging and taking supernatant after the PBS homogenate.Serum and tissue T GF-β 1 usefulness ELISA test kit detect.
The result: flavone compounds such as resveratrol and naringenin can reduce inductive type ii diabetes mice serum of streptozotocin and kidney TGF-β 1 (seeing Fig. 1 and Fig. 2), also can reduce the inductive type ii diabetes mouse blood sugar of streptozotocin (see figure 4).
Above result shows that flavone compounds such as resveratrol and naringenin have therapeutical effect to the inductive type ii diabetes of streptozotocin.
The preventive effect of the inductive mice type i diabetes of alloxan such as experimental example 3 resveratrols and naringenin
Diabetes model is set up with experiment 1, from modelling began in preceding 7 days to medicine, dosage is with experiment 1, administration every day 1 time, successive administration is to giving 2 weeks behind the alloxan, detection fasting glucose for last 1 time.
The result: flavone compounds such as resveratrol and naringenin can stop the inductive mice type i diabetes of alloxan blood sugar increasing (see figure 9).
Above result shows that flavone compounds such as resveratrol and naringenin have preventive effect to the inductive mice type i diabetes of alloxan.
Experimental example 4 resveratrols and naringenin etc. are to the preventive effect of the inductive type ii diabetes of streptozotocin
Diabetes model is set up with experiment 2, from modelling began in preceding 7 days to medicine, dosage is with experiment 2, administration every day 1 time, successive administration detects fasting glucose to giving 2 weeks behind the alloxan for last 1 time.
The result: flavone compounds such as resveratrol and naringenin can stop the inductive type ii diabetes blood sugar increasing of streptozotocin (see figure 9).
Above result shows that flavone compounds such as resveratrol and naringenin have preventive effect to the inductive type ii diabetes of streptozotocin.
Experimental example 5 resveratrols and naringenin etc. are to the influence of normal mouse sugar dosis tolerata
Use normal mouse, dosage is with experiment 2, administration every day 1 time, successive administration 10 days.More than the fasting 12h, measuring blood is counted Oh blood glucose 1 time before the administration, irritates stomach glucose 5g/kg after the administration immediately before last 1 administration, and the blood glucose when measuring 1h and 2h after the administration is sugared dosis tolerata with the blood glucose difference between 1h and the 2h.
Result: the sugared dosis tolerata (see figure 10) of the raising normal mouse that flavone compounds such as resveratrol and naringenin all can be in various degree.
Above result shows that flavone compounds such as resveratrol and naringenin have the raising effect to normal mouse sugar dosis tolerata.
Resveratrol of the present invention and naringenin can reduce TGF-β 1 level in the inductive type i diabetes mice of alloxan and inductive type ii diabetes mice serum of streptozotocin and the kidney, can also reduce inductive type i diabetes mice of alloxan and the inductive type ii diabetes mouse blood sugar of streptozotocin, improve type i diabetes mice polydipsia polyphagia symptom, and alleviate the infringement of type i diabetes mouse kidney.In addition, invent described resveratrol and naringenin and can stop inductive type i diabetes mice of alloxan and the inductive type ii diabetes mouse blood sugar of streptozotocin to raise, improve the sugared dosis tolerata of normal mouse.Above result shows that resveratrol of the present invention and naringenin have the effect of prevention and treatment diabetic nephropathy.
The following examples are used to further specify but are not limited to the present invention.
The specific embodiment
Embodiment 1: the naringenin tablet
Get naringenin 100mg/kg, add conventional adjuvant, make tablet according to common process, be used for prevention and treatment diabetic nephropathy, a day taking dose is 300-1000mg/ day.
Embodiment 2: the resveratrol capsule
Get resveratrol 50mg/kg, add conventional adjuvant, make capsule according to common process, be used for prevention and treatment diabetic nephropathy, a day taking dose is 300-1000mg/ day.
Embodiment 3: the naringenin injection
Get naringenin 100mg/kg, add conventional adjuvant, make injection according to common process, be used for prevention and treatment diabetic nephropathy, a day dosage is 5-15mg/ day.
Embodiment 4: the resveratrol injection
Get resveratrol 100mg/kg, add conventional adjuvant, make powder according to common process, be used for prevention and treatment diabetic nephropathy, a day dosage is 5-15mg/ day.
Claims (8)
1, resveratrol or the naringenin application in preparation prevention or treatment medicine for treating diabetic nephropathy.
2, application as claimed in claim 1 is characterized in that wherein said prevention or treatment diabetic nephropathy are meant the rising of the interior transforming growth factor-beta 1 level of body that the inhibition diabetes cause.
3, application as claimed in claim 1 is characterized in that wherein said prevention or treatment diabetic nephropathy are meant the blood glucose that reduces diabetics, improves diabetics polydipsia polyphagia symptom, alleviates the kidney damage of diabetics.
4, application as claimed in claim 1 is characterized in that wherein said prevention or treatment diabetic nephropathy are meant prevention diabetics blood sugar increasing, improve normal human's sugared dosis tolerata.
5,, it is characterized in that wherein said diabetic nephropathy is meant treatment type i diabetes nephropathy or type ii diabetes nephropathy as claim 1,2,3 or 4 described application.
6, application as claimed in claim 5, the route of administration of resveratrol or naringenin are oral or drug administration by injection.
7, the application of flavonoid micromolecular compound in preparation prevention or treatment medicine for treating diabetic nephropathy.
8, application as claimed in claim 7, wherein the flavonoid micromolecular compound is meant resveratrol, naringenin, naringin, hesperetin, genistein or luteolin.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101780062A (en) * | 2010-03-22 | 2010-07-21 | 张爱华 | Application of resveratrol to treating kidney disease |
| CN102000054A (en) * | 2010-10-26 | 2011-04-06 | 天津医科大学 | Flavone analog, preparation and application thereof as anti-diabetic medicament |
| CN103355665A (en) * | 2013-04-11 | 2013-10-23 | 江南大学 | Composition for regulation of blood sugar level and adjunctive treatment of diabetes mellitus |
| CN104367568A (en) * | 2014-11-18 | 2015-02-25 | 南通大学附属医院 | Application of resveratrol in preparation of medicine used for treating chronic failure |
| CN112969782A (en) * | 2018-10-26 | 2021-06-15 | 于利奇研究中心有限公司 | Method for providing malonyl-coenzyme A in coryneform bacteria and for producing polyphenols and polyketones by means of coryneform bacteria |
| CN113101295A (en) * | 2020-03-20 | 2021-07-13 | 上海疆云医疗健康科技有限公司 | Use of stilbene analogues in the treatment of diabetic renal disease |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101780062A (en) * | 2010-03-22 | 2010-07-21 | 张爱华 | Application of resveratrol to treating kidney disease |
| CN102000054A (en) * | 2010-10-26 | 2011-04-06 | 天津医科大学 | Flavone analog, preparation and application thereof as anti-diabetic medicament |
| CN102000054B (en) * | 2010-10-26 | 2014-11-05 | 天津医科大学 | Flavone analog, preparation and application thereof as anti-diabetic medicament |
| CN103355665A (en) * | 2013-04-11 | 2013-10-23 | 江南大学 | Composition for regulation of blood sugar level and adjunctive treatment of diabetes mellitus |
| CN103355665B (en) * | 2013-04-11 | 2018-08-24 | 江南大学 | A kind of composition for auxiliary hyperglycemic |
| CN104367568A (en) * | 2014-11-18 | 2015-02-25 | 南通大学附属医院 | Application of resveratrol in preparation of medicine used for treating chronic failure |
| CN112969782A (en) * | 2018-10-26 | 2021-06-15 | 于利奇研究中心有限公司 | Method for providing malonyl-coenzyme A in coryneform bacteria and for producing polyphenols and polyketones by means of coryneform bacteria |
| CN113101295A (en) * | 2020-03-20 | 2021-07-13 | 上海疆云医疗健康科技有限公司 | Use of stilbene analogues in the treatment of diabetic renal disease |
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